Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Shanghai Key Laboratory of Hydrogen Science & Center of Hydrogen Science, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
Acta Biomater. 2023 Mar 1;158:163-177. doi: 10.1016/j.actbio.2022.12.056. Epub 2022 Dec 31.
Excessive production of reactive oxygen species (ROS) amplifies pro-inflammatory pathways and exacerbates immune responses, and is a key factor in the progression of osteoarthritis (OA). Therapeutic hydrogen gas (H) with antioxidative and anti-inflammatory effects, has a potential for OA alleviation, but the targeted delivery and sustained release of H are still challenging. Herein, we develop an injectable calcium boride nanosheets (CBN) loaded hydrogel platform (CBN@GelDA hydrogel) as a high-payload and sustainable H precursor for OA treatment. The CBN@GelDA hydrogel could maintain constant physiological pH conditions which further promotes more H release than the CBN alone and lasts more than one week. The biocompatibility of this hydrogel with macrophages and chondrocytes is effectively enhanced. The experiments show that the CBN@GelDA hydrogel holds the ROS scavenging ability, reducing the expression of related inflammatory cytokines, lessening M1 macrophages but stimulating M2 phenotype, and thereby decreasing chondrocyte apoptosis, which facilitates to breaking of the vicious circle of OA progression. Furthermore, a single-time injection of the CBN@GelDA hydrogel markedly reduces joint destruction in OA rats. From what has been discussed above, this injectable spontaneous H-releasing hydrogel is promising for OA treatment. STATEMENT OF SIGNIFICANCE: Oxidative stress and inflammation play the key role in the occurrence and development of osteoarthritis (OA). The system of a hydrogel loaded with H precursor calcium boride nanosheet (CBN), which is the first to use as an H precursor, integrates superior injectable and biocompatible of hydrogel and the selection of antioxidant properties of H. This system can improve H release behavior and achieve a single injection into the articular cavity to alleviate the progression of OA in rats. This study of the combination of a convenient long-acting injectable hydrogel and a safe therapeutic gas is of great value for improving the quality of life of clinical patients.
活性氧（ROS）的过度产生会放大促炎途径并加剧免疫反应，是骨关节炎（OA）进展的关键因素。具有抗氧化和抗炎作用的治疗性氢气（H）具有缓解 OA 的潜力，但 H 的靶向输送和持续释放仍然具有挑战性。在此，我们开发了一种可注射的碳化硼纳米片（CBN）负载水凝胶平台（CBN@GelDA 水凝胶），作为 OA 治疗的高负载量和可持续 H 前体。CBN@GelDA 水凝胶可以维持恒定的生理 pH 值条件，从而促进比单独的 CBN 更多的 H 释放，持续时间超过一周。该水凝胶与巨噬细胞和软骨细胞的生物相容性得到了有效增强。实验表明，CBN@GelDA 水凝胶具有 ROS 清除能力，降低相关炎症细胞因子的表达，减少 M1 巨噬细胞但刺激 M2 表型，从而减少软骨细胞凋亡，有助于打破 OA 进展的恶性循环。此外，单次注射 CBN@GelDA 水凝胶可显著减轻 OA 大鼠的关节破坏。综上所述，这种可注射的自发 H 释放水凝胶有望用于 OA 治疗。
